Drug Shows Promise for People With Colitis, Crohn's Disease

WEDNESDAY Aug. 21, 2013 -- An experimental drug may help some people who have inflammatory bowel disease that has failed to respond to current medications, two new clinical trials find.

The drug, called vedolizumab, is being developed to treat the two main forms of inflammatory bowel disease (IBD) - ulcerative colitis and Crohn's disease. Both arise when the immune system launches an abnormal attack on the lining of the digestive tract, leading to chronic inflammation and symptoms such as abdominal cramps, diarrhea and rectal bleeding.

In the new trials, reported in the Aug. 22 issue of the New England Journal of Medicine, researchers found that vedolizumab worked in some cases where standard IBD medications had failed.

The drug was more effective for colitis than for Crohn's, however, and an expert not involved in the studies said he suspects vedolizumab might be approved for colitis first.

Overall, the results are "very exciting," said Dr. Fabio Cominelli, chief of gastroenterology and liver disease at Case Western Reserve University School of Medicine, in Cleveland.

"This is a potential new weapon in our armamentarium," said Cominelli, who wrote an editorial that accompanied the reports.

The two studies included more than 2,000 patients with either colitis or Crohn's who had failed to get enough relief from standard medications, which include immune-system suppressors such as corticosteroids, azathioprine (brand name Imuran) and mercaptopurine (Purinethol).

About half of the patients had also tried the most recently developed drugs for IBD, known as anti-TNF agents. Those drugs - infliximab (Remicade), adalimumab (Humira) and certolizumab (Cimzia) - are given intravenously, and block an inflammatory protein called tumor necrosis factor (TNF).

In one trial, nearly 900 colitis patients were given two infusions of either vedolizumab or a placebo, two weeks apart. After six weeks, 47 percent of the vedolizumab patients had a "clinical response," or a meaningful drop in their symptoms.

Those patients were then randomly assigned to either stay with the drug - getting infusions every four weeks or every eight weeks - or receive placebo infusions.

After a year, 42 percent to 45 percent of the vedolizumab patients were in remission, compared with 16 percent of the placebo group.

"The results with ulcerative colitis were really striking," said Dr. Brian Feagan, director of clinical trials at the Robarts Research Institute in London, Ontario, who worked on both studies.

The results were somewhat less impressive in the companion trial of just more than 1,100 people with Crohn's disease. In that trial, 31 percent of vedolizumab patients responded to the drug after six weeks; of those who continued with the drug, 36 percent to 39 percent were in remission after a year, compared with 22 percent of patients given placebo infusions.

It's not clear why the drug seemed to work better for colitis than Crohn's. One possibility, Cominelli said, is that people with Crohn's need longer than six weeks to show an initial response.

In contrast to colitis, which is limited to the colon, Crohn's can affect any part of the digestive tract and is generally a more extensive disease.

The colitis patients also fared better when it came to side effects. Their rates of "adverse events," such as headaches, nausea, fatigue and respiratory infections, were similar to the placebo group's.

"It seemed to have a good safety profile," Cominelli said.

In the Crohn's trial, patients on the drug were more likely to have a serious adverse event, which means anything that requires a medical intervention of some kind. Almost one-quarter of vedolizumab patients had one, compared with about 15 percent of placebo patients.

There also were four deaths in the vedolizumab group, and one in the placebo group.

It's not clear, though, that the deaths had anything to do with the drug. Feagan said the patients who died were in poor health, and since the study participants were recruited from all over the world, their general healthcare varied widely.

Takeda Pharmaceuticals, the Japanese drug manufacturer that funded the trials, has submitted vedolizumab for approval in the United States and Europe. If that happens, it's not fully clear how the drug will fit in with current colitis and Crohn's treatments.

"I don't think it should necessarily be relegated to use only after patients have tried an anti-TNF," Feagan said. A big question, he added, is whether the drug could be more helpful if used earlier on, or if given along with an anti-TNF.

Vedolizumab works by interfering with the trafficking of certain immune-system cells into the gut. That targeted action, Feagan's team said, should help limit side effects - including an increased risk of infections - caused by medications that broadly suppress the immune system.